Edathara C. Abraham, Ph.D.

Professor

Ph.D., University of Louisville, USA

sHsp/a-crystallin in congenital cataracts and neurodegenerative diseases

A major function of the α-crystallin/shsps is to interact with other crystallins and various other target proteins and prevent them from unfolding and aggregation. Thus, they have molecular chaperone-like function and play a role in maintaining eye lens transparency.  αA- and αB-crystallins and sHsps have a compact two domain structure, with a short extending carboxyl-terminal arm. Secondary structure being predominantly β-pleated sheets and stress induciblity are other common features. The αA and αB subunits of α-crystallin are expressed predominantly in the eye lens and lesser extent in the retina, spleen, thymus, brain and liver. There is involvement of αB-crystallin and hsps in major cytomorphological organization during normal growth and under pathological conditions. There is increased expression of αB-crystallin in the brain of patients with various neurodegenerative diseases.Our studies center around the belief that a structurally and functionally intact α-crystallin-molecular chaperone is essential for maintaining the eye lens transparency. Posttranslational modifications which occur during aging human eye lens are: oxidation of methionines and cysteines, glycation and crosslinking of lysine and arginine residues, and deletion of C-terminal amino acid residues. Such modifications are enhanced in diabetic lenses. We have been focusing on the role of specific C-terminal amino acid residues in the oligomeric structure, subunit interactions, and chaperone to target protein interactions. These studies are done by FRET analysis and by mammalian two hybrid assay using recombinant rat, bovine and human native and truncated constructs of αA- and αB-crystallins. We are also interested in identifying and characterizing mutations occurring in the αA-and αB-crystallin genes which cause congenital cataracts. Congenital cataracts are the major cause of blindness in infants.

Selected Publications

Anbarasu Kumarasamy and Edathara C. Abraham, Interaction of C-terminal truncated human aA-crystallins with target proteins. PLoS ONE 3(9), e3175, 2009

Latha Kallur, Atya Aziz and Edathara C. Abraham, C-terminal truncation affects subunit exchange of human aA-crystallin with aB-crystallin. Mol Cell Biochem 308; 85-91, 2008

Atya Aziz, Puttur Santhoshkumar, Krishna K. Sharma, and Edathara C. Abraham, Cleavage of the C-terminal serine of human aA- crystallin produces αA1-172  with increased chaperone activity and oligomeric size  BIOCHEMISTRY

46: 2510- 2519, 2007.

Shanthi Rajan, Reena Chandrashekar, Atya Aziz, and Edathara C. Abraham, Role of Arginine-163 and the 163-REEK-166 motif in the oligomerization of truncated aA-crystallins. BIOCHEMISTRY  45: 15684- 15691, 2006

Thampi, P. and Abraham, E.C. Influence of the C-terminal residues on oligomerization of aA-crystallin. BIOCHEMISTRY 42: 11857- 11863, 2003. [Abstract]

Bera, S., Thampi, P., Cho, W. J. and Abraham, E.C. A positive charge preservation at position 116 of aA-crystallin is  critical for its structural and functional integrity. BIOCHEMISTRY 41: 12421-12426, 2002. [Abstract]

Bera, S. and Abraham, E.C. The alphaA-crystallin R116C mutant has a higher affinity for forming  heteroaggregates with aB-crystallin. BIOCHEMISTRY 41: 297-305, 2002 [Abstract]

Shroff, N.P., Cherian, M., Bera, S. and Abraham, E.C. Mutation of R116C results in highly oligomerized aA-crystallin with modified structure and defective chaperone-like function. BIOCHEMISTRY 39: 1420-1425, 2000. [Abstract]

Cherian, M., Xiang, Y.J., Smith, J.B. and Abraham, E.C. Influence of protein-glutathione mixed disulfide on the chaperone function of alpha-crystallin. J. Biol. Chem.272:29099- 29103,1997. [Abstract]

Zhao, H., Nagaraj, R.H. and Abraham, E.C. The role of a- ands e-amino groups in the glycation-mediated cross-linking of gB-crystallin. J. Biol. Chem. 272: 14465-14469, 1997. [Abstract]

Smith, J.B, Hanson, S.R.A. Cerny, R.L. Zhao, H. and Abraham,E.C. Identification of the glycation site of lens gammaB-crystallin by fast atom bombardment tandem mass spectrometry. Anal. Biochem. 243: 186-189, 1996. [Abstract]

Casey, E.B, Zhao, H.R., and Abraham,E.C. Role of Gly-1 and Lys-2 in the glycation of bovine aB-crystallin. J. Biol. Chem. 270: 20781-20786, 1995. [Abstract]

PubMed link to additional publications